Alternative titles; symbols
HGNC Approved Gene Symbol: CISD1
Cytogenetic location: 10q21.1 Genomic coordinates (GRCh38): 10:58,269,162-58,289,586 (from NCBI)
CISD1 is a member of the CDGSH domain-containing family and may play a role in the regulation of mitochondrial oxidative capacity (Wiley et al. (2007, 2007)).
By database analysis, Wiley et al. (2007) identified CISD1, which they called MITONEET. The deduced 108-amino acid protein has a calculated molecular mass of 12.2 kD and contains an N-terminal signal sequence and a C-terminal CDGSH domain, flanked by 2 additional cysteines. The CDGSH domain contains a consensus sequence shared by CISD1, CISD2 (611507), and CISD3 (611933). Immunofluorescence studies localized CISD1 to the mitochondria. RT-PCR analysis of mouse tissues detected ubiquitous expression with highest expression in heart. Immunohistochemical staining of mouse tissues detected Cisd1 in many tissues, including liver, adipose tissue, skeletal muscle, and heart. Staining was particularly intense in cells lining the ducts and ventricles. Immunogold microscopy of rat kidney tissue, subcellular fractionation of mitochondria, and other studies further localized Cisd1 to the outer mitochondrial membrane as an integral membrane protein, oriented such that the CDGSH domain faces the cytoplasm, anchored by an N-terminal transmembrane domain.
Taminelli et al. (2008) determined that the human CISD1 protein contains a signal peptide, followed by a mitochondrial cleavage site, a CDGSH signature, and a putative nuclear localization signal, and it has several putative phosphorylation sites.
Colca et al. (2004) identified CISD1 as a binding partner for pioglitazone, a member of the thiazolidinedione (TZD) class of insulin-sensitizing drugs.
Wiley et al. (2007) noted that purified recombinant CISD1, CISD2, and CISD3 were red in color. Further analysis of metal content showed that CISD1 bound 1.6 moles of iron per mole of protein and contained no other metal content. They noted that although the CDGSH domain was initially classified as a zinc finger domain, it actually contains iron. Wiley et al. (2007) suggested that CDGSH domain-containing proteins represent an iron-containing protein family.
Wiley et al. (2007) used optical absorbance spectra, electron paramagnetic resonance, and mass spectrometry to characterize the interaction of CISD1 and iron. They determined that CISD1 binds a single 2Fe-2S cluster. Using mutation studies, they showed that amino acids cys72, cys74, cys83, and his87 form the coordinating ligands of the iron-sulfur cluster. Wiley et al. (2007) noted that the cys3-his1 coordination sphere is unusual and distinguishes CISD1 from other families of Fe-S-containing proteins.
Using differential display and RT-PCR analysis, Taminelli et al. (2008) found that the expression of CISD1 was downregulated in a tracheobronchial epithelial cell line developed from a cystic fibrosis (CF; 219700) patient in comparison with cells expressing wildtype CFTR (602421). Inhibition of CFTR chloride transport activity by CFTR inhibitors resulted in downregulation of CISD1 mRNA, and CFTR stimulation resulted upregulated CISD1 expression.
Hou et al. (2007) and Lin et al. (2007) independently determined the crystal structure of the CISD1 soluble domain (amino acids 32 to 108) to 1.8-angstrom resolution. They showed that CISD1 formed a homodimer with strong hydrophobic interactions and characterized the interactions of the cys3-his1 coordinated 2Fe-2S cluster. Lin et al. (2007) noted that UV-visible absorption spectra indicated that CISD1 can exist in oxidized and reduced states and suggested a role for CISD1 in electron transfer.
Taminelli et al. (2008) stated that the CISD1 gene maps to chromosome 10q21.1.
Wiley et al. (2007) determined that mitochondria isolated from the hearts of mice with targeted disruption of Cisd1 displayed decreased complex I-dependent oxygen consumption and decreased uncoupler-stimulated respiration compared to wildtype, suggesting that Cisd1 plays a role in regulation of mitochondrial oxidative capacity.
Colca, J. R., McDonald, W. G., Waldon, D. J., Leone, J. W., Lull, J. M., Bannow, C. A., Lund, E. T., Mathews, W. R. Identification of a novel mitochondrial protein ('mitoNEET') cross-linked specifically by a thiazolidinedione photoprobe. Am. J. Physiol. Endocr. Metab. 286: E252-60, 2004. Note: Electronic Article. [PubMed: 14570702] [Full Text: https://doi.org/10.1152/ajpendo.00424.2003]
Hou, X., Liu, R., Ross, S., Smart, E. J., Zhu, H., Gong, W. Crystallographic studies of human MitoNEET. J. Biol. Chem. 282: 33242-33246, 2007. [PubMed: 17905743] [Full Text: https://doi.org/10.1074/jbc.C700172200]
Lin, J., Zhou, T., Ye, K., Wang, J. Crystal structure of human mitoNEET reveals distinct groups of iron-sulfur proteins. Proc. Nat. Acad. Sci. 104: 14640-14645, 2007. [PubMed: 17766439] [Full Text: https://doi.org/10.1073/pnas.0702426104]
Taminelli, G. L., Sotomayor, V., Valdivieso, A. G., Teiber, M. L., Marin, M. C., Santa-Coloma, T. A. CISD1 codifies a mitochondrial protein upregulated by the CFTR channel. Biochem. Biophys. Res. Commun. 365: 856-862, 2008. [PubMed: 18047834] [Full Text: https://doi.org/10.1016/j.bbrc.2007.11.076]
Wiley, S. E., Murphy, A. N., Ross, S. A., van der Geer, P., Dixon, J. E. MitoNEET is an iron-containing outer mitochondrial membrane protein that regulates oxidative capacity. Proc. Nat. Acad. Sci. 104: 5318-5323, 2007. [PubMed: 17376863] [Full Text: https://doi.org/10.1073/pnas.0701078104]
Wiley, S. E., Paddock, M. L., Abresch, E. C., Gross, L., van der Geer, P., Nechushtai, R., Murphy, A. N., Jennings, P. A., Dixon, J. E. The outer mitochondrial membrane protein mitoNEET contains a novel redox-active 2Fe-2S cluster. J. Biol. Chem. 282: 23745-23749, 2007. [PubMed: 17584744] [Full Text: https://doi.org/10.1074/jbc.C700107200]